Omeprazole and Rilpivirine: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 2, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Rilpivirine
Omeprazole
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
Let's talk about taking rilpivirine (Edurant, or Juluca) together with omeprazole (Prilosec). Rilpivirine is an HIV medicine that only gets absorbed well when your stomach is acidic. Omeprazole works by lowering stomach acid, which is great for heartburn but it means your body soaks up much less of the rilpivirine.
When rilpivirine levels drop, the HIV medicine may stop working, and the virus could even become resistant to it. Because of this, these two are not meant to be used together. Please don't change anything on your own, but do talk with your pharmacist or doctor. There are safe options they can pick for your stomach.
Interaction: Omeprazole (PPI) markedly raises gastric pH, reducing dissolution and absorption of oral rilpivirine, whose bioavailability is pH-dependent. Result: decreased rilpivirine AUC/Cmax, loss of virologic response, and risk of resistance.
- Direction: reduced rilpivirine exposure/efficacy (PK-based absorption effect)
- Severity: contraindicated
- Onset: delayed (virologic failure develops over time)
- Evidence: probable
Management: Avoid combining. PPIs are contraindicated with rilpivirine and separated dosing does not overcome the effect. Substitute a non-interacting acid-suppression strategy per prescriber, or reassess the antiretroviral regimen. Neither agent is a prodrug requiring activation.
What happens
Reduced oral rilpivirine exposure, reduced efficacy of rilpivirine and an increased loss of virologic response
Interaction Deep Dive
The combined use of proton pump inhibitors with oral rilpivirine or products that contain rilpivirine is contraindicated. Because proton pump inhibitors raise gastric pH, giving them together with oral rilpivirine can diminish the absorption of rilpivirine, which in turn lowers rilpivirine plasma levels, causes loss of virologic response, and may lead to the development of resistance1234.
Why it happens (mechanism)
Reduced absorption of oral rilpivirine due to increased gastric pH caused by proton pump inhibitors
How to manage this interaction
Keep taking both medicines exactly as prescribed until you speak with your care team, but this pairing does need a change because the two are not recommended together.
- Tell your pharmacist and HIV provider that you are on (or being offered) omeprazole while taking rilpivirine.
- Your team may switch you to a different heartburn or reflux option that does not lower stomach acid the same way, since spacing the doses apart is not enough to fix this.
- Mention any over-the-counter Prilosec OTC too, since people often buy it themselves.
Your care team can manage this safely by choosing an alternative that keeps your HIV treatment working.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) In drug interaction trials, giving omeprazole together with rilpivirine to healthy volunteers or to antiretroviral treatment-naive patients with HIV-1 produced a significant reduction in rilpivirine AUC, Cmax, and Cmin. Subjects took once daily doses of omeprazole 20 mg along with rilpivirine 150 mg. For rilpivirine, the ratio estimate (omeprazole plus rilpivirine versus rilpivirine alone) was 0.6 (90% CI, 0.51 to 0.71) for AUC, 0.6 (90% CI, 0.48 to 0.73) for Cmax, and 0.67 (90% CI, 0.58 to 0.78) for Cmin 23.
b) After multiple doses of rilpivirine (150 mg daily) combined with omeprazole (20 mg daily), rilpivirine AUC fell by 40%, Cmax fell by 40%, and Cmin fell by 33% 4.
Common questions
Can I take Omeprazole and Rilpivirine together?
Omeprazole lowers stomach acid and blocks absorption of rilpivirine, which can cause HIV treatment failure and resistance, so this combination should be avoided. Do not stop either drug on your own; ask your pharmacist or HIV provider about a safer acid-reducing option. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Omeprazole and Rilpivirine interaction?
It is rated contraindicated. These should generally not be used together.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How is the Omeprazole and Rilpivirine interaction managed?
Keep taking both medicines exactly as prescribed until you speak with your care team, but this pairing does need a change because the two are not recommended together. Tell your pharmacist and HIV provider that you are on (or being offered) omeprazole while taking rilpivirine. Your team may switch you to a different heartburn or reflux option that does not lower stomach acid the same way, since sp… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Omeprazole or Rilpivirine need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (4)
- Product Information: JULUCA oral tablets, dolutegravir rilpivirine oral tablets. ViiV Healthcare (per FDA), Research Triangle Park, NC, 2022. DailyMed
- Product Information: EDURANT(R) oral tablets, rilpivirine oral tablets. Janssen Therapeutics (per FDA), Horsham, Pa, 2024. DailyMed
- Product Information: EDURANT(R) PED oral tablets for suspension, rilpivirine oral tablets for suspension. Janssen Therapeutics (per FDA), Horsham, Pa, 2024. DailyMed
- Product Information: KONVOMEP(TM) powder for oral suspension, omeprazole sodium bicarbonate powder for oral suspension. Azurity Pharmaceuticals Inc (per manufacturer), Woburn, MA, 2022. DailyMed
Keep reading about Rilpivirine
Keep reading about Omeprazole
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Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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